Unraveling the vaginal microbiota-based etiology of recurrent cystitis: the potential role of <i>Lactobacillus</i> vaginal suppositories

Recurrent cystitis is a common problem in women that substantially impairs quality of life and contributes to increasing healthcare costs. Traditionally regarded as an ascending infection originating from the gut, recurrent cystitis is now increasingly understood as a disorder rooted in vaginal dysbiosis, with the vagina acting as a key reservoir for uropathogenic Escherichia coli . Loss of a Lactobacillus -dominant vaginal microbiota and overgrowth of enteric and anaerobic bacteria are strongly associated with recurrent cystitis, particularly in postmenopausal women. Lactobacillus species promote vaginal health by producing lactic acid, maintaining a low pH, generating antimicrobial compounds, inhibiting pathogen adhesion, and modulating mucosal immune responses. At the same time, long-term antimicrobial prophylaxis, although effective in reducing recurrences, is limited by adverse effects and the promotion of antimicrobial resistance. These concerns have driven interest in strategies that restore the protective vaginal ecosystem rather than relying on repeated antimicrobial exposure. This narrative review summarizes current concepts linking vaginal dysbiosis to recurrent cystitis, highlights the protective role of Lactobacillus , and synthesizes clinical data on Lactobacillus vaginal suppositories, particularly Lactobacillus crispatus ( L. crispatus )-based preparations, as a targeted, non-antimicrobial prophylactic option. Across pilot, phase II, and randomized trials, Lactobacillus vaginal therapy has demonstrated a generally favorable safety and tolerability profile, with preliminary evidence suggesting a potential to reduce recurrent cystitis episodes while restoring a Lactobacillus -dominant vaginal microbiota. However, larger, standardized studies are still needed. Collectively, these findings provide a rationale for investigating Lactobacillus vaginal suppositories as a microbiome-informed, non-antimicrobial strategy for the long-term prevention of recurrent cystitis, particularly in postmenopausal and other high-risk women, and highlight the importance of further research to define the role of vaginal microbiota-directed therapies in future recurrent cystitis management.